We have assembled a group of investigators from different disciplines to focus on the problems of disease caused by herpesviruses, especially problems underlying latency and oncogenesis. Several herpesviruses of animals and man have been chosen to attack differing aspects of the ability of these viruses to cause latent infection and to transform cells to malignancy. We hope to determine under what conditions latency and reactivation of these viruses occur, the molecular events required to initiate and maintain the transformed state of mammalian cells, the events that influence the ability of the transformed cells to metastasize, and the role of these viruses in neoplastic disease of the human urogenital tract. Studies concerning the transformation of human and other cells by herpesviruses will be conducted by Dr. Fred Rapp. Attempts to delineate the gene and gene products that are responsible for initiation and maintenance of the transformed state will be conducted by Dr. Mary K. Howett. Dr. S. S. Tevethia will examine the involvement of herpes simplex virus (HSV) glycoproteins in cell-mediated immune cytolysis. Dr. Marquez's efforts will be to characterize these HSV glycoproteins in immune complexes. Drs. Geder and Hyman will study infectious bovine rhinotracheitis virus to determine whether the genes responsible for transformation by this virus share sequences with human cytomegalovirus (CMV) and whether there are common genes required for transformation. Dr. Mary Judith Tevethia will attempt to genetically characterize the CMV genome, including gene(s) required for in vitro transformation of mammalian cells. Cloning of HSV and CMV DNA fragments is being supported by Dr. John Taylor. The guinea pig and its cells are being used as a model system by Dr. Harriet Isom, who plans to study transformation using guinea pig CMV, and Dr. Richard Tenser who will study latency. A direct attack on the problem of etiology of human neoplastic diseases by herpesviruses will be carried out by Dr. Hyman to determine whether herpesvirus nucleic acids are present in human cancer tissues.